Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA
Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA
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DOI：
10.1074/jbc.m211311200
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发表时间：
2003-07-25
影响因子：
4.8
通讯作者：
Reichert, AS
中科院分区：
文献类型：
--
作者：
Herlan, M;Vogel, F;Reichert, AS
线粒体的结构是高度动态的，取决于融合和裂变过程的平衡。酵母中线粒体动力蛋白 Mgm1 的缺失会导致线粒体广泛断裂和线粒体 DNA 丢失。 Mgm1 及其人类直系同源物 OPA1 与人类 I 型视神经萎缩相关，被认为参与线粒体的裂变或融合，或者参与线粒体内膜的重塑和嵴形成（Wong, E. D.、Wagner, J. A.、Gorsich, S. W.、McCaffery, J. M.、Shaw, J. M. 和 Nunnari, J. (2000) J.细胞生物学. 151, 341-352;Wong, E. D., Wagner, J. A., Scott, S. V., Okreglak, V., Holewinske, T. J., Cassidy-Stone, A., 和 Nunnari, J. (2003) J. Cell Biol. 160, 303-311; Yaffe, M. P. 和 Jensen, R. E. (2003) Mol Biol.，出版中）。 Mgm1 及其直系同源物以两种不同长度的形式存在。为了获得对其生物发生和功能的新见解，我们对这些亚型进行了表征。大亚型 (L-Mgm1) 包含 N 端假定的跨膜片段，而短亚型 (s-Mgm1) 中不存在该片段。大亚型是面向膜间隙的完整内膜蛋白。此外，发现 l-Mgm1 向 s-Mgm1 的转化依赖于 Pcp1 (Mdm37/YGR101w)，这是最近发现的野生型线粒体形态所必需的成分。 Pcp1 是 Rhomboid 的同源物，Rhomboid 是一种已知参与果蝇细胞间信号传导的丝氨酸蛋白酶，表明 Pcp1 在 Mgm1 蛋白水解成熟过程中发挥作用。 s-Mgm1 的表达可以部分补充 Deltapcp1 表型。两种同工型的表达（但不能单独表达任何一种同工型）能够部分补充 Deltamgm1 表型。因此，Pcp1 对 l-Mgm1 的加工以及 Mgm1 两种亚型的存在对于野生型线粒体形态和线粒体 DNA 的维持至关重要。
The structure of mitochondria is highly dynamic and depends on the balance of fusion and fission processes. Deletion of the mitochondrial dynamin-like protein Mgm1 in yeast leads to extensive fragmentation of mitochondria and loss of mitochondrial DNA. Mgm1 and its human ortholog OPA1, associated with optic atrophy type I in humans, were proposed to be involved in fission or fusion of mitochondria or, alternatively, in remodeling of the mitochondrial inner membrane and cristae formation (Wong, E. D., Wagner, J. A., Gorsich, S. W., McCaffery, J. M., Shaw, J. M., and Nunnari, J. (2000) J. Cell Biol. 151, 341-352; Wong, E. D., Wagner, J. A., Scott, S. V., Okreglak, V., Holewinske, T. J., Cassidy-Stone, A., and Nunnari, J. (2003) J. Cell Biol. 160, 303-311; Sesaki, H., Southard, S. M., Yaffe, M. P., and Jensen, R. E. (2003) Mol. Biol. Cell, in press). Mgm1 and its orthologs exist in two forms of different lengths. To obtain new insights into their biogenesis and function, we have characterized these isoforms. The large isoform (L-Mgm1) contains an N-terminal putative transmembrane segment that is absent in the short isoform (s-Mgm1). The large isoform is an integral inner membrane protein facing the intermembrane space. Furthermore, the conversion of l-Mgm1 into s-Mgm1 was found to be dependent on Pcp1 (Mdm37/YGR101w) a recently identified component essential for wild type mitochondrial morphology. Pcp1 is a homolog of Rhomboid, a serine protease known to be involved in intercellular signaling in Drosophila melanogaster, suggesting a function of Pcp1 in the proteolytic maturation process of Mgm1. Expression of s-Mgm1 can partially complement the Deltapcp1 phenotype. Expression of both isoforms but not of either isoform alone was able to partially complement the Deltamgm1 phenotype. Therefore, processing of l-Mgm1 by Pcp1 and the presence of both isoforms of Mgm1 appear crucial for wild type mitochondrial morphology and maintenance of mitochondrial DNA.